October 23, 2014

The skin is an important major organ, the function of which includes acting as a protective covering against injury for underlying tissue, as well as a sensing, cooling, and water retention among others.  Now German researchers have discovered that there is an odor receptor expressed in at least keratinocytes, a major skin cell type, and that this receptor, when stimulated, activates a number of cellular pathways that lead to important skin repair.

To find the human skin odor receptor, the scientists used a microarray “chip” to analyze the RNA of skin cells cultured from humans (which are called “primary” cells), focusing exclusively on seeking nucleic acids that bear a resemblance to known olfactory receptors (smell receptors).  RNA is ribonucleic acid, and is the underlying chemical of the form of genes in between DNA and its final protein form.  Of the top 8 candidates found, the scientists confirmed 5 were truly expressed with PCR, a more sensitive experimental method.

But the researchers still did not know what kind of chemicals, or “smells”, would activate the newly found smell receptor.  To embark on the search they genetically engineered a specific found receptor, OR2AT4, into a type of cell used specifically for experiments.  The researchers then stimulated the genetically engineered cell with over 100 different odorants, and identified “Sandalore”, a synthetic sandalwood-like smell molecule, as one that activated the OR2AT4 receptor through a fluorescent label again engineered into the cells.

The protein form of OR2AT4 was confirmed to be present in samples of human skin cells.  Applying Sandalore to the natural human skin cells turned on important signaling pathways, and was further confirmed by shut-off of the same pathways when the OR2AT4 was turned off using a method called RNA interference.

Experiments showed that exposing the human skin cells to Sandalore caused the cells to proliferate (or multiply) 32% more than unexposed cells.  The exposed cells also exhibited “migration”, or enhanced movement.  The combination of proliferation and migration is a strong sign that the wound-repair pathways were being activated.  When the skin is injured, new skin cells must undergo motion to the edge of the injury to grow.  Indeed, an experimentally set-up “wound scratch” assay showed that in laboratory conditions, the skin cells after exposure to Sandalore closed up artificially induced wounds quickly.

However the discovery is not inconsistent with observations of the developmental history of at least one nonhuman organism.  In the western clawed frog, during the larval stage, gene expression of an odor receptor was identified in skin cells as well.  Unlike the most recent discovery though, in the adult frog the odor receptor disappears from the skin and reappears only in the olfactory cavity.

The research was published on Aug 7 2014, in the Journal of Investigative Dermatology


*Journal of Investigative Dermatology (2014) 134, 2823–2832; doi:10.1038/jid.2014.273

(Image Credits: photo by Luke Price, CC-BY-2.0)